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Biomedical subjects

L Lanier

Publications and source records attributed to L Lanier.

At least 19 recordsLinked to original sources

Stereotactic core biopsy reduces the reexcision rate and the cost of mammographically detected cancer.

The management of patients with mammographic abnormalities is rapidly shifting from needle-localized surgical biopsy (NLB) to stereotactic core biopsy (SCB). The precise role of SCB in the management of nonpalpable breast cancer remains to be defined. The purpose of this study was to compare SCB to NLB in the diagnosis of mammographically detected breast cancer in women who underwent breast-conserving surgery. The records of all patients with nonpalpable breast cancer who underwent breast-conserving surgery from 1/1/95 to 6/1/97 were analyzed with respect to method of diagnosis, time interval from detection to diagnosis and breast-conserving surgery, volume of breast tissue excised, margin status and reexcision rate, number of surgical procedures, and total charges and costs per patient. During a 30-month period, 117 patients with nonpalpable breast cancer underwent breast-conserving surgery. The diagnosis was made by NLB in 69 patients and SCB in 48 patients. The time from detection to diagnosis and breast-conserving surgery was 1.7 +/- 0.5 and 8.1 +/- 1.2 days for SCB patients and 6. 8 +/- 1.3 and 16.9 +/- 2.3 days for NLB patients (P < 0.01). The volume of breast tissue removed was 117.9 +/- 5.6 cm3 for SCB patients versus 75.2 +/- 2.9 cm3 for NLB patients (P < 0.01). Three SCB patients (6%) had positive margins, while 38 NLB patients (55%) had positive margins (P < 0.01). Only 1 SCB patient (2%) was reexcised, while 34 NLB patients (50%) were reexcised (P < 0.01). Eighty-nine percent of SCB patients had a single surgical procedure compared to 39% of NLB patients (P < 0.001). Patients who underwent SCB had reduced total charges and total costs per patient compared to NLB patients ($11,700 +/- $554 and $3537 +/- $167 per SCB patient versus $15,654 +/- $706 and $4853 +/- $198 per NLB patient, P < 0. 0001). Stereotactic core biopsy shortens the time from detection at mammography to diagnosis and breast-conserving therapy, permits appropriate discussion of treatment alternatives, reduces the positive margin rate and reexcision rate, and may represent a significant cost savings in the management of nonpalpable breast cancer.

Biopsy, Needle↗

Learning radiology from interactive videodiscs: bar-code book versus computer-assisted instruction.

RATIONALE AND OBJECTIVES: We compared an interactive videodisc with bar-code book with an interactive videodisc with computer-assisted instruction for learning radiology to determine whether there would be differences in instructional effectiveness, instruction time, or subjective preference. METHODS: Two different videodisc modules were created. Each was presented in two formats with identical content: bar-code book and computer-assisted instruction. In a controlled crossover experimental design, 48 fourth-year medical students were assigned one bar-code book module and one computer module. Pre- and posttests were administered. RESULTS: Mean scores improved from pretest to posttest after students used the modules in either format (p < .01). There were no significant differences between students who used the bar-code book and those who used the computer in pretest scores, posttest scores, gains in score from pretest to posttest, or instruction time for either module. Subjectively, 74% of the students preferred computer-assisted instruction, 20% preferred bar-code book, and 7% preferred neither. CONCLUSION: Although bar-code book and computer versions of an interactive videodisc can be educationally equivalent, most students preferred the computer. When videodisc is being integrated into the curriculum, the choice between bar-code book and computer-assisted instruction can be made on the basis of noneducational factors such as cost and availability.

CD-I↗

B7 and interleukin 12 cooperate for proliferation and interferon gamma production by mouse T helper clones that are unresponsive to B7 costimulation.

We have previously shown that dendritic cells isolated after overnight culture, which can express B7 and are potent stimulators of naive T cell proliferation, are relatively poor at inducing the proliferation of a panel of murine T helper 1 (Th1) clones. Maximal stimulation of Th1 clones was achieved using unseparated splenic antigen presenting cells (APC). An explanation for these findings is provided in the present study where we show that FcR+ L cells transfected with B7 stimulate minimal proliferation of Th1 clones in response to anti-CD3 antibodies, in contrast to induction of significant proliferation of naive T cells. However, addition of interleukin 12 (IL-12) to cultures of Th1 cells stimulated with anti-CD3 and FcR+ B7 transfectants resulted in a very pronounced increase in proliferation and interferon gamma (IFN-gamma) production. Exogenous IL-12 did not affect the B7-induced proliferation of naive T cells. This showed that whereas costimulatory signals delivered via B7-CD28 interaction are sufficient to induce significant proliferation of naive T cells activated through occupancy of the T cell receptor, Th1 T cell clones require cooperative costimulation by B7 and IL-12. This costimulation was shown to be specific by inhibition of proliferation and IFN-gamma production using chimeric soluble cytolytic T lymphocyte-associated antigen 4-human IgG1Fc (CTLA4-Ig) and anti-IL-12 antibodies. Furthermore, the significant antigen specific proliferation and IFN-gamma production by Th1 clones observed when splenocytes were used as APC was almost completely abrogated using CTLA4-Ig and anti-IL-12 antibodies. Thus two costimulatory signals, B7 and IL-12, account for the ability of splenic APC to induce maximal stimulation of Th1 clones. IL-10 downregulates the expression of IL-12 by IFN-gamma-stimulated macrophages and this may account largely for t the ability of IL-10 to inhibit APC function of splenic and macrophage APC for the induction of Th1 cell proliferation and IFN-gamma production. Indeed we show that IL-12 can overcome the inhibitory effect of IL-10 for the APC-dependent induction of proliferation and IFN-gamma production by Th1 clones. These results suggest that proliferation by terminally differentiated Th1 clones, in contrast to naive T cells, requires stimulation via membrane-bound B7 and a cytokine, IL-12. It is possible that these signals may result in the activation of unresponsive T cells during an inflammatory response. IL-10, by its role in regulating such innate inflammatory responses, may thus help to maintain these T cells in an unresponsive state.

Abatacept↗

Breast implants, common complications, and concurrent breast disease.

Recent concern regarding breast implants has emphasized the special imaging needs of the approximately 2 million American women who currently have prosthetic breast implants, including silicone gel, silicone gel with a textured silicone coating, saline, biocompatible gel, polyurethane-coated, double-lumen, and tissue expanders. Both palpable and nonpalpable breast lesions can occur in patients with implants, and these lesions must be evaluated in the same manner as in patients without implants, which presents a challenge for the mammographer. Not only is the breast tissue of a patient with implants more difficult to image, but the patient may have complications from the implants. The major complications of their use involve hematoma in the early postoperative period, infection, capsule contracture, rupture, and silicone granulomas. Familiarity with the more common types of implants, the possible complications of their use, and concurrent breast disease may help improve diagnosis in these patients.

Adult↗

Radiologic anatomy--a credit course for first-year medical students.

Diagnostic radiology should assume a more prominent role in medical student education. We have developed a 4-year plan for radiologic education at the University of Florida. The initial step in this plan is a required credit course in radiologic anatomy given in the first semester. Designed to introduce students to various imaging modalities while teaching anatomic recognition, the course combines a lecture series with systematized self-study film packets and self-test packets. These are reinforced by a videotape series and other written materials. Examinations are in practical format utilizing radiographs on viewbox stations. The course provides a foundation for subsequent coursework in diagnostic radiology, including radiologic pathology and clinical radiology. These courses stress how to workup patients and how to use the radiologist as a consultant in patient care. The response to the radiologic anatomy course has been highly favorable.

Anatomy↗

Phantom evaluation of imaging modalities for silicone breast implants.

RATIONALE AND OBJECTIVES: Recent concern regarding possible adverse effects from silicone breast implants has increased the role of radiologists in assessing augmented breasts. The authors compare the commonly available imaging modalities in evaluating the intact silicone implant as well as free silicone in the adjacent tissue. METHODS: A contrast resolution phantom and breast of veal phantom were tested. Fat was used as a reference material. The phantoms were imaged with xeromammography, film-screen mammography, ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Proton MRI spectroscopy also was performed on fat, silicone, water, and water/gelatin samples. The consensus of two radiologists determined whether free silicone was present. RESULTS: CT and MRI provided the best images of the implant and the free silicone. Several features of MRI were useful: spin-density scans and the fast low-angle shot (FLASH) and fast imaging with steady-state precision (FISP) techniques provided excellent resolution, a consistent chemical shift artifact appeared around the silicone, and frequency selective pre-saturation techniques resulted in marked suppression of the silicone. CONCLUSION: Additional testing in a more realistic setting, breast coil design, and improvement of various MRI techniques, particularly the frequency selective pre-saturation techniques, all appear promising in evaluating breast implants, the presence of free silicone, and the adjacent tissues.

Breast↗

Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering.

We have examined the functional consequences of mutations present in defective alleles of the retinoblastoma susceptibility gene (RB1) isolated from two spontaneously arising tumors. Unlike cDNA clones expressing the wild-type protein p110Rb, those encoding the two mutant proteins failed to induce the appearance of senescent cells in transfected Saos-2 human osteosarcoma cells. The mutant proteins were also defective in binding to the E1A oncoprotein, were unable to become hyperphosphorylated, and failed to become tightly associated with nuclear structures. We conclude that mutations in two distinct regions of the protein concomitantly affect these four aspects of p110Rb function.

Adenovirus Early Proteins↗

Selective generation of erythroid burst-promoting activity by recombinant interleukin 2-stimulated human T lymphocytes and natural killer cells.

Because T lymphocytes and natural killer (NK) cells produce a variety of growth factors and interleukin 2 (IL2) modulates the activity of both, we assessed the ability of IL2 to stimulate human T cells and NK cells to produce hematopoietic growth factors detectable in clonogenic marrow culture. Human recombinant interleukin 2 (rIL2) added directly to cultures of human bone marrow that had been depleted of monocytes or depleted of both monocytes and T cells caused no significant alteration of myeloid (CFU-GM) or erythroid colony formation. Conditioned media harvested from rIL2-stimulated (greater than 100 U/mL) peripheral blood mononuclear cells, T cells, Leu-2 cells, and Leu-3 cells all had erythroid burst-promoting activity (BPA) but lacked myeloid colony-stimulating factor (GM-CSF) or CFU-GM-inhibitory activity. These T cells were IL2 receptor-negative, and the addition of anti-IL2 receptor monoclonal antibody (anti-Tac) to T cell cultures did not abrogate this IL2-stimulated BPA production. In addition, Percoll gradient-enriched, large granular lymphocytes (LGL) were separated by fluorescence-activated cell sorting into Leu-11+ (NK) cells and Leu-11- (low-density Leu-4+ T) cell fractions. rIL2 stimulated LGL, Leu-11+ and Leu-11- cells to produce BPA but not detectable GM-CSF or CFU-GM-inhibitory activity. Leu-11+ (NK) cells were Tac-negative from days 0 through 14 of culture. We conclude that rIL2 at high concentrations stimulated T cells, Leu-2 and Leu-3 cell subsets, LGL, and NK cells to produce BPA but not GM-CSF and that this stimulation may be mediated by an IL2 receptor distinct from Tac or by an epitope of the IL2 receptor not recognized by the anti-Tac antibody.

Antibodies, Monoclonal↗

Comparison of T cell receptor gene rearrangements in patients with large granular T cell leukemia and Felty's syndrome.

Felty's syndrome (FS) refers to the occurrence of rheumatoid arthritis, splenomegaly, and neutropenia. A subset of these patients has recently been described with a chronic T cell leukemia of large granular lymphocytes (LGCL). To examine the spectrum of lymphocyte abnormalities in FS and LGCL, we examined phenotypic and genotypic properties of lymphocytes from eight FS patients. In two of these FS patients, we observed an elevated proportion of T cells with an unusual phenotype (CD3+/Leu-7+/Leu-8-/CR3+) (46 +/- 5% of mononuclear cells). The FS lymphocytes had large granular morphology on Wright-Giemsa stain and were active in antibody-dependent cellular cytotoxic activity. This phenotype, morphology, and activity was similar to LGCL patients except that the latter T cells additionally expressed the Fc-IgG receptor recognized by monoclonal antibody Leu-11 (CD 15). In the remaining six FS patients, the proportion of CD3+/Leu-7+/CR 3+ T cells was only 10 +/- 8%, which was not significantly different from age-matched normal subjects (6.6 +/- 2.2%). To determine the clonality of T lymphocytes in FS and LGCL, we examined DNA for rearrangements of the T cell antigen receptor beta-chain (Ti beta) and gamma-chain (Ti gamma) genes by using Southern blotting techniques. We found a clonal rearrangement of the Ti beta 1 and Ti gamma genes in both LGCL patients. In contrast, no clonal rearrangements of Ti beta or Ti gamma genes were detected in lymphocytes from the FS patients. These results indicate that FS patients are heterogeneous in their phenotype and that one subset exhibits polyclonal expansion of an unusual lymphocyte subset.

Antibody-Dependent Cell Cytotoxicity↗

Reversal of experimental allergic encephalomyelitis with monoclonal antibody to a T-cell subset marker.

Administration of a monoclonal antibody (GK1.5) that recognizes the L3T4 marker present on helper T cells prevented the development of experimental allergic encephalomyelitis (EAE) in mice. Furthermore, treatment with GK1.5 reversed EAE when the antibody was given to paralyzed animals. In vivo injection of GK1.5 selectively reduced the number of L3T4+ cells in the spleen and the lymph nodes. These results suggest that manipulation of the human equivalent of the murine L3T4+ T-cell subset with monoclonal antibodies may provide effective therapy for certain autoimmune diseases.

Animals↗

Regulation of expression of class II major histocompatibility antigens on human peripheral blood monocytes and Langerhans cells by interferon.

Although normal peripheral blood monocytes from different individuals are primarily DR+ (L243), they vary in the mean expression of L243 and the percentage of cells with detectable Leu-10 (DC/DS) and L03 (D). All three species of human recombinant IFNs enhance Ia expression on normal peripheral blood monocytes; however, r-IFN-gamma is much more effective in enhancing the expression of these three class II antigens in vitro than r-IFN-beta or r-IFN-alpha A. In addition, r-IFN-gamma has a more profound effect on the expression of Leu-10 (DC/DS), an antigen critical for presentation in autologous MLR, than on L243 (DR). Adherent monocytes cultured for 5 days develop macrophage characteristics and become strongly positive for all three of these class II antigens without further manipulation. Isolated skin Langerhans cells which are thought to be antigen presenting cells in the epidermis are also strongly positive for all three of these Ia antigens and are unaffected by IFN treatment. Therefore, this early interferon effect on cell surface expression may be the result of enhancing the maturation of monocytes to mature antigen presenting cells.

Adult↗

The murine T cell antigen receptor and associated structures.

The immunochemical approach described in this review has led to the identification of a new component of the T cell surface, the disulfide-linked heterodimer, which has many of the properties expected of a molecule with antigen-specific receptor activity: 1) Expression of the heterodimer is restricted to T cells. 2) The molecule expresses clonotypic epitopes presumably related to the specific antigen recognition site, as well as crossreactive epitopes associated with the molecular framework. 3) At the primary sequence level, the molecule has regions of constant as well as variable structure. The numerous observations from other laboratories that clonotypic antibodies which inhibit antigen-specific reactions are directed against similar disulfide-linked heterodimers provide compelling evidence that this structure is in fact the T cell antigen receptor. Two important conclusions can be drawn from the results of peptide analysis of the receptor subunits. First, the molecular fingerprints of the alpha and beta chains are very different, indicating that the subunits are encoded by different genes. Second, both subunits have constant and variable regions, suggesting that both subunits play a role in producing the antigen combining site. A crucial question that remains to be answered is whether the same or different combining sites are responsible for recognition of antigen and the MHC restricting element. The recent report by Marrack et al. (1983b) that the receptors of two independent T cell hybridomas with the same antigen and MHC specificities expressed the same clonotypic determinant and yielded identical peptide maps (Kappler et al. 1983) provides strong evidence that the heterodimer is responsible for both antigen and MHC recognition. If this is the case, it remains to be determined whether a single site contributed by both subunits recognizes antigen and MHC, or whether one subunit contributes a site for MHC recognition and the other a site for antigen recognition. If, however, as Parham (1984) has recently proposed, conserved rather than polymorphic regions of the MHC product are recognized in MHC restriction, it is possible that the heterodimer functions solely in recognition of antigen, and the restriction may be provided by accessory proteins in a receptor complex. Definitive conclusions as to the role of the individual chains will probably require construction of functional T cells using molecular clones of the genes encoding the receptor and accessory proteins. Recently, the molecular cloning of cDNA encoding putative T cell receptors has been reported from murine (Hedrick et al. 1984) and human (Yanagi et al. 1984) cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗